Method for determining the composition of a reaction system

Abstract

A computer-implemented method which comprises the automated and rational (computer aided) modification of chemical recipes, in particular the design of the concrete starting composition of a reaction system, for example an oligomeric or polymeric polyol system, using an optimization procedure aiming at maximizing the similarity to an original target/reference system is provided. Furthermore, a data processing apparatus comprising means for carrying out the method, a computer program product comprising instructions which, when the program is executed by a computer, cause the computer to carry out the method and a computer-readable storage medium comprising instructions which, when executed by a computer, cause the computer to carry out the method is provided.

1 . A computer-implemented method for designing a starting composition of a chemical reaction system for maximizing similarity to a reference reaction system in order to substitute individual components in the reference system, the method comprising:
 A) providing information on a reference reaction system, the information comprising components of the reference reaction system and their relative amounts in the reference reaction system;   B) providing information on a test reaction system, the information comprising components of the test reaction system and their relative amounts in the test reaction system;   C) providing at least one first rule for forming and/or cleaving chemical bonds from the components of the reference reaction system and/or species formed from components of the reference reaction system;   D) applying the at least one first rule on the reference reaction system, thereby obtaining a modified reference reaction system;   E) providing at least one descriptor for at least part of the modified reference reaction system and for at least part of a modified test reaction system as recited in step H);   F) determining descriptor value(s) from the at least one descriptor for at least part of the modified reference reaction system;   G) providing at least one second rule for forming and/or cleaving chemical bonds from the components of the test reaction system and/or species formed from components of the test reaction system;   H) applying the at least one second rule on the test reaction system, thereby obtaining a modified test reaction system;   I) determining descriptor value(s) from the at least one descriptor as recited in step E) for at least part of the modified test reaction system;   J) determining the distance and/or the dissimilarity between the descriptor values from steps F) and I) using a measure for the distance in a descriptor space occupied by the at least one descriptor;   K) deciding to adapt or not to adapt the test reaction system depending on the result of the determination of the distance and/or dissimilarity in step J); and   L) if the decision to adapt in step K) has been taken, adapting the test reaction system by changing the components of and/or their relative amounts in the test reaction system yielding an updated test reaction system and subsequently repeating the method starting at step H) based on the updated test reaction system.   
     
     
         2 . The method according to  claim 1 , wherein the components of the reference reaction system as recited in step A) and/or the components of the test reaction system as recited in step B) comprise alkylene oxides, polyfunctional carboxylic acids, carboxylic acid anhydrides, cyclic ethers, carbon dioxide, cyclic carbonates, polyols, polyisocyanates, polyamines, aromatic hydrocarbons, olefins, (meth)acrylates, bisphenols, phosgene, dialkyl carbonates, aldehydes, lactames, glycolides, amino acids, hydroxy-substituted carboxylic acids, or a combination of at least two of the aforementioned components. 
     
     
         3 . The method according to  claim 1 , wherein the at least one first rule recited in C) and/or the at least one second rule recited in G) comprises which functional group of a component is present, which functional group of a component is available for forming a covalent bond or for cleaving a covalent bond, which functional groups of components can react with other functional groups, a threshold criterion when the forming or the cleavage of a covalent bond occurs, or a combination of at least two of the aforementioned rules. 
     
     
         4 . The method according to  claim 1 , wherein the at least one first rule of step C) is identical to the at least one second rule of step G). 
     
     
         5 . The method according to  claim 1 , wherein applying the at least one first rule as recited in step D) and/or applying the at least one second rule as recited in step H) comprises running a kinetic Monte Carlo-simulation, running a molecular Monte Carlo-simulation, running a molecular dynamics simulation, running a Miller-Macosko type calculation, or a combination of at least two of the aforementioned simulations. 
     
     
         6 . The method according to  claim 1 , wherein the modified reference reaction system comprises an ensemble of discrete components and information on the discrete components of the modified reference reaction system and their relative amounts in the modified reference reaction system. 
     
     
         7 . The method according to  claim 1 , wherein the modified test reaction system comprises an ensemble of discrete components and information on the discrete components of the modified test reaction system and their relative amounts in the modified test reaction system. 
     
     
         8 . The method according to  claim 1 , wherein the at least one descriptor as recited in step E) is:
 a statistical/compositional descriptor; and/or   a topological descriptor;   a molecular descriptor;   a force field based descriptor;   a quantum chemical descriptor;   a thermodynamic descriptor;   a health, sustainability or environment related descriptor;   or a combination of at least two of the aforementioned descriptors.   
     
     
         9 . The method according to  claim 1 , wherein the distance and/or dissimilarity as recited in step J) comprises the euclidean/L2 distance, the manhattan/L1/cityblock distance, Canberra distance, Chebyshev distance, Mahalanobis distance, Minkowski distance, Rogers-Tanimoto dissimilarity, Russell-Rao dissimilarity, Sokal-Michener dissimilarity, Sokal-Sneath, mean absolute percentage error, Yule dissimilarity, cosine dissimilarity, dice dissimilarity, or a combination of at least one of the aforementioned distances and/or dissimilarities. 
     
     
         10 . The method according to  claim 1 , wherein the decision as recited in step K) comprises one or more of the following a decision criteria:
 a threshold value for the distance and/or dissimilarity in step J),   a threshold value for the change in distance and/or dissimilarity relative to one or more previously executed steps J),   a threshold value for the execution time for the method,   a threshold value for the number of repetitions of the method, and   a threshold value for at least one of the descriptors.   
     
     
         11 . The method according to  claim 1 , wherein adapting the test reaction system by changing the components of the test reaction system and/or their relative amounts in the test reaction system as recited in step L) comprises executing an algorithm selected from: random search, grid search, Bayesian optimization, simplex optimization, evolutionary optimization, genetic algorithm, particle swarm optimization, Metropolis-Hastings Markov-chain Monte-Carlo, adaptive Markov-chain Monte-Carlo, simulated annealing, parallel tempering, mixed linear and non-linear programming, or a combination of at least two of the aforementioned algorithms. 
     
     
         12 . The method according to  claim 1 , further comprising communicating a final test reaction system to a user if the decision has been taken in step K) not to adapt the test reaction system in step K). 
     
     
         13 . A data processing apparatus comprising means for carrying out the method of  claim 1 . 
     
     
         14 . A computer program product comprising instructions which, when the program is executed by a computer, cause the computer to carry out the method of  claim 1 . 
     
     
         15 . A computer-readable storage medium comprising instructions which, when executed by a computer, cause the computer to carry out the method of  claim 1 . 
     
     
         16 . The method of  claim 6 , wherein determining descriptor value(s) from the at least one descriptor for at least part of the modified reference reaction system in step F) is carried out using atomistic resolution information for each discrete component. 
     
     
         17 . The method of  claim 7 , wherein determining descriptor value(s) from the at least one descriptor for at least part of the modified test reaction system in step I) is carried out using atomistic resolution information for each discrete component. 
     
     
         18 . The method according to  claim 8 , wherein:
 the statistical/compositional descriptor comprises at least one descriptor selected from the group consisting of number average molecular weight, weight average molecular weight, viscosity average molecular weight, polydispersity index, mean functionality, OH number, and acid number;   the topological descriptor comprises at least one descriptor selected from the group consisting of Wiener Index, Randic connectivity index, Balaban-J index, Ipc index, Zagreb index, Bertz index, chi molecular connectivity indices, Kier-Hall valence connectivity index, seniority and priority indices, kappa shape indices, BCUT indices, Estate indices, Walk and path counts, and extended connectivity fingerprints;   the molecular descriptor comprises at least one descriptor selected from the group consisting of Labute's approximate surface area, solvent-accessible surface area, radius of gyration, 2D autocorrelations, Eigenvalue-based descriptors, RDF descriptors, 3D-MORSE descriptors, WHIM descriptors, GETAWAY descriptors, functional group counts, number of rotatable bonds, number of hydrogen acceptors and donors, Gasteiger/Marsili Partial Charges, topological polar surface area, and molar refractivity;   the force field based descriptor comprises at least one descriptor selected from the group consisting of intramolecular potential energy, radial distribution function, bond angle distribution function, and dihedral distribution functions;   the quantum chemical descriptor comprises at least one descriptor selected from the group consisting of atomic charges, HOMO and LUMO energies, molecular hardness, molecular polarizability, dipole moment, total energy, and molecular quantum number descriptor;   the thermodynamic descriptor comprises at least one descriptor selected from the group consisting of octanol-water partition coefficient, sigma-profile, sigma moment, polarity moment vector, activity coefficient, chemical potential, free energy, octanol-water partition coefficient, and solubility; and/or   the health, sustainability or environment related descriptor comprises at least one descriptor selected from the group consisting of toxicity, carbon dioxide equivalents, carbon footprint, energy consumption, product recycling rate, sustainability index, supply chain miles, water footprint, and price.